Classic treatments for Parkinson's disease include drug therapy, deep brain stimulation, and physiotherapy. Conventional drug treatmentsThe following products, aimed at mitigating motor symptomatology, are as follows:
L-DOPA (levodopa). Precursor of dopamine synthesis. From a therapeutic perspective, the introduction of levodopa (L-DOPA) in 1960 represented a breakthrough in the treatment of PD, and it remains the most effective symptomatic therapy in Parkinsonian disorders. However, chronic administration of L-DOPA and other antiparkinsonian drugs causes serious side effects that should have special attention paid to them by the medical community. Due to this, new compounds devoid of psychomotor, biochemical, neuropsychiatric, and autonomic complications are under experimental scrutiny in preclinical studies and clinical trials.
Dopaminergic agonists (amantadine, apomorphine, bromocriptine, cabergoline, lisuride, pergolide, pramipexole, ropinirole, rotigotine). They are useful in monotherapy in early stages of the disease or in association with levodopa, as they have less risk of developing motor complications than levodopa.
Monoamine oxidase inhibitors, MAOIs (selegiline, rasagiline).
Catechol-O-methyltransferase (COMT) inhibitors (entacapone, tolcapone). These drugs reduce the metabolism of levodopa and therefore increase its half-life and therapeutic effects, reducing the need for levodopa by up to 30%.
One of the most relevant complications of chronic treatment with L-DOPA and other dopaminergic agents is the "wearing-off" phenomenon, characterized by motor fluctuations and dyskinesia.
To circumvent this problem, complementary strategies have been developed with dopaminergic and non-dopaminergic agents, such as new formulations of L-DOPA, COMT inhibitors (opicapone), dopaminergic agonists, adenosine A2A antagonists (istradephylline, preladenant, tozadenant), glutamatergic antangonists (NMDA, N-methyl-d-aspartate), serotonergic agents (eltoprazine), and mGluR5 glutamate receptor modulators (mavoglurant). However, none of these agents have been shown to be sufficiently effective.
Polypharmacy with antidepressants, antipsychotics, urological agents, analgesics, antihistamines, and acetylcholinesterase inhibitors contribute to the development of complications, undesirable drug interactions, and anticholinergic conditions. In addition, there are gastrointestinal complications (constipation, hypersalivation, dysphagia, chewing difficulties), cardiovascular problems, neuroendocrine disturbances, and psychiatric disorders associated with chronic use of conventional antiparkinsonian drugs.
An additional complication is Pisa syndrome, which is characterised by a sustained abnormal posture with flexion of the body and head to one side and axial rotation of the trunk and is associated with the use of antipsychotics.
A bad habit in the management of psychotic symptoms in Parkinsonian patients is the administration of atypical neuroleptics (such as quetiapine), which contribute to aggravating motor symptoms, due to their antidopaminergic effect, and to increasing the side effects intrinsic to the antipsychotic agents themselves.
In order to provide effective medical treatment, the main objective is to provide the patient with control of signs and symptoms for as long as possible and to minimise adverse effects.
Symptomatic drug therapies usually provide some control over the motor signs of PD for the 4-6 years of life following diagnosis, mainly through the use of levodopa/carbidopa as a standard prescription for symptomatic treatment, while monoamine oxidase-B (MAO) inhibitor drugs may be considered more effective for treatment in the early stages of the disease.
However, other dopamine agonists (e.g., ropinirole, pramipexole) can be used as a monotherapy in early disease and as moderately effective adjuvant therapy in advanced stages of the disease. To minimise tremor symptoms, a second line of anticholinergic agents (e.g., trihexyphenidyl, benztropine) are also commonly prescribed.